Rad51 protein function. 2A and B, p .

Rad51 protein function. UniProt is the world's leading high-quality, comprehensive and freely accessible resource of protein sequence and functional information. Dec 10, 2020 · RAD51-associated protein 1 (RAD51AP1) is a key protein in the homologous recombination (HR) DNA repair pathway. The Rad51 protein is highly conserved in all eukaryotes for which sequence information is available. RAD51 Rad51, a central HR protein, is a homolog of RecA that binds the single-strand tail of a processed DNA end to form a nucleoprotein filament. RAD51 and its gene family are key regulators of DNA fidelity through diverse roles in double-strand break repair, replication stress, and meiosis. Silencing RAD51 or BRCA2 stimulated both SSA and A-EJ, but not C-NHEJ, validating the two-step model. One of the key players in this essential function is the RAD51 protein, a crucial component in the homologous recombination repair (HRR) pathway. Not surprisingly, Rad51 is also involved in repair The RAD51 protein binds to the DNA at the site of a break and encases it in a protein sheath, which is an essential first step in the repair process. Here, we use a separation-of-function allele of RAD51 that Jun 8, 2006 · Introduction Human RAD51 is a homologue of the Escherichia coli RecA protein and is known to function in recombinational repair of double-stranded DNA breaks. Here, we report an unexpected function of RAD51 in the maintenance methylation of genomic DNA, a function that is separable from its role in homologous recombination. Thus, regulating Rad51 activity could be an attractive target. Oct 1, 2023 · Numerous lines of evidence substantiate the essentiality of the function performed by this protein. The recombination function of RAD51 requires its binding to single-stranded DNA (ssDNA), whereas binding to dsDNA is inhibitory. . Both the activator protein Swi5/Sfr1 and Ca2+ ions stimulate different reaction steps and induce The Rad51 protein is highly conserved in all eukaryotes for which sequence information is available. We show that mutating Rad51 Ser 192 to Ala or Glu confers hypersensitivity to DNA damage and homologous General model for RAD51 protein function in DNA replication: (A) RAD51 escorts the replisome and binds ssDNA. 9% (Fig. These proteins have been found to form two distinct complexes in vivo, Oct 6, 2022 · Summary RAD51 and the breast cancer suppressor BRCA2 have critical functions in DNA double-strand (dsDNA) break repair by homologous recombination and the protection of newly replicated DNA from nucleolytic degradation. Indeed, Rad51 deficient yeast and mouse trophoblast-like cells exhibit closely similar defects, including increased sensitivity to ionising radiation and chromosome loss, both of which can be explained by compromised DSB repair 19, 25, 31. Dec 3, 2018 · Here, we review recent structural and functional studies of RAD51, the protein that catalyzes the defining step of homologous recombination: homology recognition and DNA strand exchange. The RAD51 protein attaches (binds) to the DNA at the site of a break and encases it in a Jul 7, 2022 · Rad51 is a DNA-binding protein, which can regulate nucleases, helicases, DNA translocases, and signaling proteins to function as a regulator of replication stress, such as mediating fork reversal and restoring repaired forks (4). AI generated definition based on: Methods in Enzymology, 2018 Sep 12, 2018 · It has long been appreciated that the particular structural features of filaments formed by recombinase proteins like RAD51 reflect its function. May 1, 2021 · As the primary catalyst of homologous recombination (HR) in vertebrates, RAD51 has been extensively studied in the context of repair of double-stranded DNA breaks (DSBs). Dec 5, 2024 · RAD51 recombinase is a key protein involved in homologous recombination, the most faithful repair process for a double-stranded DNA (dsDNA) break (1 – 3). Understanding mechanistic details of Rad51 in homologous recombination (HR) and rep … Rad51 protein is a protein involved in DNA repair that forms filaments and can be removed by the monomer Srs2 to measure the time taken for filament removal. In model organisms, RAD51 paralogs are RAD51 mediator proteins that structurally resemble RAD51 and promote its HR activity. We found that RADX stimulates RAD51-dependent ATP hydrolysis and identified a direct protein-protein interaction between RADX and RAD51 mediated by the oligosaccharide binding domain-3 (OB3) of RADX. Feb 3, 2025 · We also examined published cryo-EM structures of human RAD51 structures with ssDNA or dsDNA, derived from imposing helical symmetry, based on the high structure and function conservation of yeast and human Rad51 proteins. cerevisiae is 59% identical to the human and mouse proteins and 30% identical to RecA, the most important protein for homologous recombination in bacteria. Here, we show that in response to DNA damage, budding yeast Rad51 is phosphorylated on Ser 192 in a manner that is primarily mediated by the DNA-damage-responsive protein kinase Mec1. Mutations in the lower eukaryotic homologues of RAD51 result in a deficiency in the repair of double-stranded DNA breaks. Nov 11, 2016 · Because upregulation of RAD51 in cancer cells can promote tumor resistance to DNA-damaging oncologic therapies, we and others have worked to develop cancer therapeutics that target various aspects of RAD51 protein function. RAD51 together with its meiosis specific homolog DMC1 also perform analogous functions in meiotic recombination when parental homologous chromosomes pair and recombine (4). Rad51 is expressed in proliferating cells with the highest expression in S or S/G2 phase of the cell cycle [24–26]. Abstract Rad51 is a key enzyme involved in DNA double-strand break repair by homologous recombination. Learn about this gene and related health conditions. Recombinase nucleoprotein filaments are arranged with proteins in a right-handed helix around DNA. Sep 10, 2021 · RAD51 is a well known player of DNA repair and homologous recombination. We identified a novel role for RAD51 in innate immune response signaling. The RAD51–single stranded DNA (ssDNA) filament catalyzes the Jul 17, 2025 · Complete information for RAD51B gene (Protein Coding), RAD51 Paralog B, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium RAD51 (BRCC5, FANCR, HsRad51, HsT16930, RAD51A, RECA) protein expression summary. With recent advances in the understanding of RAD51 function extending beyond DSBs, the importance of RAD51 throughout DNA metabolism has become increasingly clear. BRCA2 recruits RAD51 to sites of DNA damage through interaction with eight conserved motifs of approximately 35 amino acids, the BRC repeats; however, the specific function of each repeat remains unclear. coli RecA protein, is central to HR-mediated DSB repair. Additional RAD51 interactions and functions may be revealed. Defects in RAD51 lead to the accumulation of self-DNA in the cytoplasm, triggering a STING-mediated innate immune response after replication stress and BRCA2 has an essential function in DNA repair by homologous recombination, interacting with RAD51 via short motifs in the middle and at the C terminus of BRCA2. Jan 1, 2002 · Abstract. May 17, 2024 · Latest News Function of RAD51 protein in repairing double-strand DNA breaks on chromosomes clarified by the University of Tokyo — Opening a path to understanding cancer development 2024. The function of Rad51 p was predicted by its structural homology to the bacterial DNA repair protein RecA and the T4 phage protein UvsX (3, 8 The Rad51 protein is highly conserved in all eukaryotes for which sequence information is available. In this chapter, we describe our cryo-EM approach to capture the human RAD51 filament structures in various stages of catalysis. May 4, 2010 · Here, we have examined the role of RAD51 in the only plant that exhibits high GT frequencies, the model bryophyte Physcomitrella patens. These proteins regulate nucleases, helicases, DNA translocases, and Oct 26, 2020 · The human protein Rad51 is double-edged in cancer contexts: on one hand, preventing tumourigenesis by eliminating potentially carcinogenic DNA damage and, on the other, promoting tumours by introducing new mutations. In non-irradiated cells, comparing with p53-proficient cells, the percentage of cells containing Rad51 foci formation in p53-deficient cells was significantly elevated to 21. Specific mutations can be linked to structural changes and known essential functions. The Rad51 protein shows homology to E. Human Rad51 protein (HsRad51)-promoted DNA strand exchange, a crucial step in homologous recombination, is regulated by proteins and calcium ions. In this study, we report for the first time the presence of the Rad51 recombinase as well as the Rad51C and Xrcc3 paralog proteins in mitochondria of cultured human cells. GeneCards - The Human Gene Compendium May 28, 2018 · Replication protein A (RPA) and RAD51 are DNA-binding proteins that help maintain genome stability during DNA replication. Rad51 is the key enzyme for homologous recombination, an evolutionarily conserved mechanism for the repair of DNA damage and the generation of genetic diversity. Here, we report that a conserved 36 Feb 8, 2022 · Here, we addressed the mechanisms by which RAD51 regulates this second step, preventing nonconservative repair in human cells. 05. The recombination-independent function of BRCA2 is stimulated by the C-terminal fragment of the breast cancer suppressor BRCA2. Normal Function The RAD51 gene provides instructions for making a protein that is essential for repairing damaged DNA. Jan 3, 2001 · RAD51 is only involved in DSB repair via synthesis-dependent strand annealing (SDSA) and is not involved in DSB repair via break-induced replication (BIR) or single-strand annealing (SSA) (reviewed in 9). Given the observation that many tumors become resistant to radiation therapy and DNA-damaging chemotherapeutics and also that tumor cell populations can acquire a high number of genetic alterations and then expand clonally To examine whether p53-inhibited hyper-recombination is Rad51 dependent, Rad51 foci formation was tested after loss of p53 function by immunostaining. 2A and B, p RAD51 is a protein that plays a crucial role in the repair of double-strand breaks in DNA through homologous recombination, facilitating DNA strand exchange and searching for homology in an ATP-dependent manner. , homology search and in strand exchange with a homologous DNA partner, almost no inactivating mutations of RAD51 have been associated with cancer predisposition; on the contrary, overexpression of RAD51 is associated with a poor prognosis in different types of tumours. These proteins have been found to form two distinct complexes in vivo, Mar 4, 2021 · Here, we sought to understand how RADX regulates RAD51 and DNA replication. Find diseases associated with this biological target and compounds tested against it in bioassay experiments. Orthologs of the yeast RAD51 gene have been identified in various organisms, including humans [7], and rad51 mutants display replication defects and chromosomal instability both in yeast and human cells [8, 9]. e. This study shows the cryo-EM structure of an ADP-bound RAD51 double-filament that wraps around ssDNA revealing a stepwise Jul 29, 2018 · Symbol, synonyms, gene family about RAD51 and general information of RAD51 protein,antibody,gene, et al. Jan 1, 2018 · In particular, recent technical breakthroughs in cryo-EM have made it possible to define the structure and function of human RAD51 at near-atomic resolution. In addition, Rad51 promotes mitochondrial DNA synthesis when replication stress is increased. The recent identification of the RAD51 protein, a eukaryotic homologue of Escherichia coli RecA, represents a landmark discovery in our … UniProt is the world's leading high-quality, comprehensive and freely accessible resource of protein sequence and functional information. The interactions of RADX with RAD51 and ssDNA inhibit RAD51 nucleofilament formation and filament-mediated processes Rad51 filament formation and strand invasion is regulated by many mediator proteins such as the Rad51 paralogues and the Shu complex, consisting of a Shu2/SWS1 family member and additional Rad51 paralogues. Apr 7, 2025 · The BRCA1 protein is normally found in the cells of breast and other tissues, where it plays a role in several important cellular functions, including transcription, DNA repair, and cell cycle control. All proteins of this family include an ATPase Walker motif in their catalytic domain, however eukaryotic Rad51 Mar 8, 2025 · Gene target information for RAD51 - RAD51 recombinase (human). AI generated definition based on: European Journal of Pharmacology Aug 1, 1997 · The human Rad51 protein is a structural homolog of Escherichia coli RecA. The human protein Rad51 is double-edged in cancer contexts: on one hand, preventing tumourigenesis by eliminating potentially carcinogenic DNA damage and, on the other, promoting tumours by introducing new mutations. Maintaining appropriate levels of RAD51 expression and activity is critical for HR and thus cancer prevention. RPA, the eukaryotic ssDNA binding protein, stimulates DNA strand exchange by removing secondary structures from ssDNA during presynaptic complex Feb 21, 2017 · Abstract RAD51, a multifunctional protein, plays a central role in DNA replication and homologous recombination repair, and is known to be involved in cancer development. The function of Rad51 p was predicted by its structural homology to the bacterial DNA repair protein RecA and the T4 phage protein UvsX (3, 8 Jul 17, 2025 · Complete information for RAD51D gene (Protein Coding), RAD51 Paralog D, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium While loss or reduction of RAD51 protein function can increase cancer risk, RAD51 upregulation in cancer can also contribute to therapeutic resistance (8, 9). Jun 21, 2023 · The BRCA2 tumour suppressor protein—the product of BRCA2—is well characterized, but the cellular functions of the RAD51 paralogues remain unclear. Aug 21, 2024 · The human Shu complex promotes homologous recombination by regulating RAD51. The sequential assembly and disassembly of Rad51 to the broken DNA ends depend on reversible protein-protein interactions. Rad51 forms nucleo-protein filaments on single-stranded DNA and mediates homologous pairing and strand exchange between DNA duplexes [7–9]. Understanding mechanistic details of Rad51 in homologous recombination (HR) and repair could facilitate design of novel methods, including CRISPR, for Rad51-targeted cancer Feb 10, 2023 · RAD51 is a highly conserved recombinase which serves crucial functions in the cell through its role in DNA damage repair (homologous recombination, HR) and in replication fork protection. Function In humans, RAD51 is a 339- amino acid protein that plays a major role in homologous recombination of DNA during double strand break repair. It is involved in mediating resistance to PARP inhibitors in breast cancer cells, regardless of BRCA mutation status. Breaks also occur when chromosomes exchange genetic material in preparation for cell division. We observe a DNA damage-induced increase in mitochondrial levels of each protein as well as an oxidative stress-induced increase in the physical association of Rad51 with mtDNA. RAD51 has the function of finding and invading homologous DNA sequences to enable accurate and timely DNA repair. Our results show that the two RAD51 proteins have partially redundant functions in the maintenance of genome integrity and resistance to ionizing radiation. Defects in As the primary catalyst of homologous recombination (HR) in vertebrates, RAD51 has been extensively studied in the context of repair of double-stranded DNA breaks (DSBs). Like RecA, Rad51 mediates homologous pairing and DNA strand exchange in the synaptic phase. Two papers provide new insight into the Mar 28, 2018 · High protein sequence conservation suggests that the function of Rad51 is also conserved. Here the authors reveal that the Shu complex proteins, SWSAP1-SWS1, decorate the RAD51 filament on ssDNA and facilitate May 6, 2002 · . Loss of RAD51 function would therefore be expected to result in an elevated mutation rate, leading to accumulation Surprisingly, although RAD51 plays a pivotal role in HR, i. However, recent reports that transgenic mice lacking the RAD51 gene die early in development suggest an additional and essential function Mar 27, 2019 · Rad51-mediated homologous recombination is the major mechanism for repairing DNA double-strand break (DSB) repair in cancer cells. Here the authors reveal a function for RAD51 in protecting under-replicated DNA in mitotic human cells, promoting mitotic PALB2, a chromatin associated protein, links BRCA2 to upstream signalling BRCA1 and helps guide RAD51 to sites of DNA damage 34 – 36. The mutant allele is expressed at the mRNA and protein levels (Figure S1A-D), although the mutant is much less abundant than the WT RAD51 on the protein level (Figure 1C, S1C-D). In this repair process, an ATP-dependent DNA strand exchange takes place in which a template strand invades base-paired strands of homologous DNA molecules. RAD51, a multifunctional protein, plays a central role in DNA replication and homologous recombination repair, and is known to be involved in cancer development. AI generated definition based on: European Journal of Pharmacology Rad51 binds to single-stranded DNA (ssDNA) to form the presynaptic filament that promotes a homology search and DNA strand exchange, and Rad54 stimulates the strand-pairing function of Rad51. May 21, 2007 · Cooperation between the DNA recombinase RAD51 and the breast cancer susceptibility protein BRCA2 is crucial for the repair of double-strand DNA breaks. 17 Here we present the isolation of a Rad51/RecA protein homolog from the archaeon Sulfolobus solfataricus, and show that this protein, RadA, possesses the characteristics of a DNA strand exchange protein: The RadA protein is a DNA-dependent ATPase, forms a nucleoprotein filament on DNA, and catalyzes DNA pairing and strand exchange. In the nucleus of many types of normal cells, BRCA1 interacts with RAD51 to repair DNA double-strand breaks, which can be caused by natural radiation or other exposures, as well as during Sep 28, 2016 · Rad51 is a conserved eukaryotic protein that mediates the homologous recombination repair of DNA double-strand breaks that occur during mitosis and meiosis. For example, Rad51p from S. The Rad51–ssDNA complex, with the help of Rad54, performs the homology search to bind a homologous template and helps restore any lost information caused by the DSB. The RAD51 protein is recruited onto the DNA break by BRCA2 and forms homopolymeric filaments that invade the homologous chromatid and use it as a templa … May 17, 2024 · Latest News Function of RAD51 protein in repairing double-strand DNA breaks on chromosomes clarified by the University of Tokyo — Opening a path to understanding cancer development 2024. Sep 25, 2020 · While loss or reduction of RAD51 protein function can increase cancer risk, RAD51 upregulation in cancer can also contribute to therapeutic resistance (8, 9). In HR, RAD51 (with the help of mediators and paralogs) forms a nucleoprotein filament on the single-stranded DNA produced via resection of a double-stranded Jun 11, 2021 · The RAD51 recombinase is a critical effector of Homologous Recombination (HR), which is an essential DNA repair mechanism for double-strand breaks. Substances DNA-Binding Proteins Rad51 Recombinase RAD51B protein, human RAD51C protein, human RAD51D protein, human XRCC2 protein, human Tumor Suppressor Proteins Poly (ADP-ribose) Polymerase Inhibitors Multiprotein Complexes The RAD51 mediators function to nucleate, elongate, stabilize, and disassemble RAD51 during repair. Jul 6, 2011 · The function of BRCA2 in recombination is to control RAD51, a protein that catalyzes homologous pairing and DNA strand exchange. With recent advances in the understanding of RAD51 function extending beyond Sep 10, 2021 · RAD51 is a well known player of DNA repair and homologous recombination. Here we review the suggested roles of RAD51 beyond HR Total levels of RAD51 in the RA2630 cell lines are comparable to those in the wild type BJ fibroblasts (Figure 1B). All proteins of this family include an ATPase Walker motif in their catalytic domain, however eukaryotic Rad51 Substances DNA-Binding Proteins Rad51 Recombinase RAD51B protein, human RAD51C protein, human RAD51D protein, human XRCC2 protein, human Tumor Suppressor Proteins Poly (ADP-ribose) Polymerase Inhibitors Multiprotein Complexes The RAD51 mediators function to nucleate, elongate, stabilize, and disassemble RAD51 during repair. The RAD51 protein is recruited onto the DNA break by BRCA2 and forms homopolymeric filaments that invade the homologous chromatid and use it as a template for repair. coli RecA and forms similar nucleoprotein filaments on ssDNA in the presynaptic phase of homologous recombination. New functions for the RAD51 paralogs during replication and in RAD51 filament flexibility have recently been uncovered. Here, we discovered that a dynamic interaction with molecular chaperone Hsp90 Abstract The human tumor suppressor protein BRCA2 plays a key role in recombinational DNA repair. Its accumulation on DNA might be increased by obstacles that transiently block Aug 17, 2023 · RAD51 filaments are essential for eukaryotic homologous recombination. RAD51C binds XRCC3 (CX3) to form a heterodimer, and separately with RAD51B to combine with Eukaryotic cells possess several mechanisms for repairing double-stranded breaks in DNA. Dec 2, 2024 · Abstract RAD51 is related to the bacterial RecA protein and is best known for its role in homologous recombination-mediated repair of DNA damage. The RAD51 gene provides instructions for making a protein that is essential for repairing damaged DNA. All proteins of this family include an ATPase Walker motif in their catalytic domain, however eukaryotic Rad51 RAD51 and its gene family are key regulators of DNA fidelity through diverse roles in double-strand break repair, replication stress, and meiosis. RAD51AP1 physically interacts with the RAD51 recombinase and promotes RAD51-mediated capture of donor DNA, synaptic complex assembly, and displacement-loop formation when tested with nucleosome-free DNA Sep 27, 2019 · The central recombination enzyme RAD51 has been implicated in replication fork processing and restart in response to replication stress. Jun 1, 2025 · Through molecular dynamics simulations and protein structure network analysis, we seek to elucidate the binding modes of these inhibitors and their effects on Rad51 function. Sep 6, 2022 · Halder et al. Mar 4, 2021 · Here, we sought to understand how RADX regulates RAD51 and DNA replication. Three different RAD51 dominant-negative forms (DN-RAD51s) repressed GC and stimulated SSA/A-EJ. show that RAD51 protects nascent DNA from unscheduled nucleolytic degradation through its binding to double-stranded DNA. In the nucleus of many types of normal cells, the RAD51 protein interacts with many other proteins, including BRCA1 and BRCA2, to fix damaged DNA. RAD51 filaments are detectable by immunofluorescence as distinct foci in the cell Jul 17, 2025 · Complete information for RAD51 gene (Protein Coding), RAD51 Recombinase, including: function, proteins, disorders, pathways, orthologs, and expression. RAD51 is an ATPase that forms a nucleoprotein filament on single-stranded DNA. Jul 24, 2023 · ATP binding is essential for protein interaction and complex formation with other RAD51 paralogs 6,10,11. Rad51-mediated homologous recombination is the major mechanism for repairing DNA double-strand break (DSB) repair in cancer cells. We have previously shown that the Rad51-I345T protein has higher affinity for DNA than wild-type Rad51 (17). To test the activity of other gain-of-function alleles, the Rad51-V328A and Rad51-P339S proteins were purified, and their activities compared with Rad51-I345T and wild-type Rad51 (Figure 1 A). Loss of RAD51AP1 leads to defective HR, genome instability, and telomere erosion. The exact role of human Rad51 within the cell is poorly understood but, like its bacterial and yeast homologs, hRad51 is believed to play a central role in homologous recombination. Exposure to radiation, ultraviolet light, or certain chemicals can cause breaks in DNA. RAD51 modulators, therefore, emerge as significant tools, not only in understanding RAD51 is a protein that plays a crucial role in the repair of double-strand breaks in DNA through homologous recombination, facilitating DNA strand exchange and searching for homology in an ATP-dependent manner. Rad51, the homolog of the E. One mechanism involves genetic recombination with an intact sister duplex. The five human Rad51 paralogs are suggested to play an important role in the maintenance of genome stability through their function in DNA double-strand break repair. Jun 11, 2021 · The RAD51 recombinase is a critical effector of Homologous Recombination (HR), which is an essential DNA repair mechanism for double-strand breaks. In contrast, the precise role of the five RAD51 paralogs is unknown. Given the observation that many tumors become resistant to radiation therapy and DNA-damaging chemotherapeutics and also that tumor cell populations can acquire a high number of genetic alterations and then expand clonally Jun 25, 2024 · Introduction to RAD51 modulators The intricate dance of DNA within our cells is a marvel of biological engineering, and at its heart lies the process of DNA repair. egh 8msh vr qd7t op1tlj gfiyasm 1bsv flfz upn5p edrhaa1x